The use of membrane chromatography or normal flow membrane based adsorbers is well known; see U.S. Pat. No. 4,895,806 and Membrane Chromatography: Preparation and Applications to Protein Separation, Zeng, X, Biotechnol. Prog 1999, vol 15, p. 1003-1019.
All of these devices are basically formed of a housing having an inlet and an outlet and one or more layers of an adsorptive membrane located between the inlet and outlet such that all liquid entering the inlet must flow through the one or more membrane layers before reaching the outlet. The membranes are typically rendered adsorptive by surface modification, in situ copolymerization or grafting, direct formation from adsorptive materials or by the inclusion of adsorptive particles (such as chromatography media) in the membrane matrix during formation of the membrane. In this way, one or more constituents of the liquid stream are bound to the membrane surface and removed from the stream. After completion of the filtration step, the bound material is then eluted by adding a different solution or changing pH conditions or by other well known methods in the art and either disposed of or processed and used for whatever purpose.
Typically, the material removed is the protein of interest. The remainder of the materials in the stream, such as viruses, endotoxins, nucleic acids, host cell proteins and the like pass through the device unhindered and are removed from the system.
Some have suggested removing the trace contaminants such as viruses, endotoxins, nucleic acids, host cell proteins and the like from the stream instead of removing the protein of interest. Traditionally, this has been done through the use of chromatography columns containing media with quaternary amine chemistry. This approach has several advantages such as higher yields of the product of interest. However, it has several disadvantages. For one, the use of columns results in a significant underutilization of the capacity of the column components, typically less than 1%. Moreover, the process is time consuming often taking hours to complete due in large part to long residence time required for the stream to be in the presence of the chromatography media. Lastly, the cost of the media, additional buffers, along with the QC and validation costs associated with their use, significantly impact the economics of using chromatography columns for this application.
The potential of using membrane-based adsorbers in lieu of chromatography media has been mentioned to overcome the above problems. However, the current devices have their own set of problems that need to be overcome. The problem with these devices has been that they are not efficient and are therefore expensive to make and operate. The mere adding of layers does not increase the efficiency. Instead it merely adds to the expense of the manufacture of the device and its operation. Some have tried various flow distribution devices such as tapered end plates and screens similar to what is traditionally used in chromatography columns to improve efficiency. Yet the overall results have not been satisfactory.
What is needed is a membrane adsorber device that is efficient, utilizes its capacity, has high throughput and preferably is disposable so as to eliminate the need for cleaning and revalidation of the device before reuse. The present invention provides such a membrane and device, especially for trace contamination removal.